Influence of pre-treatment structural brain measures on effects of action-based cognitive remediation on executive function in partially or fully remitted patients with bipolar disorder.

Cognitive impairment is an emerging treatment target in patients with bipolar disorder (BD) but so far, no evidence-based treatment options are available. Recent studies indicate promising effects of Cognitive Remediation (CR) interventions, but it is unclear who responds most to these interventions. This report aimed to investigate whether pre-treatment dorsal prefrontal cortex (dPFC) thickness predicts improvement of executive function in response to Action-Based Cognitive Remediation (ABCR) in patients with BD. Complete baseline magnetic resonance imaging (MRI) data were available from 45 partially or fully remitted patients with BD from our randomized controlled ABCR trial (ABCR: n = 25, control group: n = 20). We performed cortical reconstruction and volumetric segmentation using FreeSurfer. Multiple linear regression analysis was conducted to assess the influence of dPFC thickness on ABCR-related executive function improvement, reflected by change in the One Touch Stocking of Cambridge performance from baseline to post-treatment. We also conducted whole brain vertex wise analysis for exploratory purposes. Groups were well-matched for demographic and clinical variables. Less pre-treatment dPFC thickness was associated with greater effect of ABCR on executive function (p = 0.02). Further, whole-brain vertex analysis revealed an association between smaller pre-treatment superior temporal gyrus volume and greater ABCR-related executive function improvement. The observed associations suggest that structural abnormalities in dPFC and superior temporal gyrus are key neurocircuitry treatment targets for CR interventions that target impaired executive function in BD.

Recent advances in solid oxide cell technology for electrolysis.

In a world powered by intermittent renewable energy, electrolyzers will play a central role in converting electrical energy into chemical energy, thereby decoupling the production of transport fuels and chemicals from today's fossil resources and decreasing the reliance on bioenergy. Solid oxide electrolysis cells (SOECs) offer two major advantages over alternative electrolysis technologies. First, their high operating temperatures result in favorable thermodynamics and reaction kinetics, enabling unrivaled conversion efficiencies. Second, SOECs can be thermally integrated with downstream chemical syntheses, such as the production of methanol, dimethyl ether, synthetic fuels, or ammonia. SOEC technology has witnessed tremendous improvements during the past 10 to 15 years and is approaching maturity, driven by advances at the cell, stack, and system levels.

Genomic alterations accompanying tumour evolution in colorectal cancer: tracking the differences between primary tumours and synchronous liver metastases by whole-exome sequencing.

BACKGROUND: Colorectal cancer (CRC) patients with metastatic disease can become cured if neoadjuvant treatment can enable a resection. The search for predictive biomarkers is often performed on primary tumours tissue. In order to assess the effectiveness of tailored treatment in regard to the primary tumour the differences in the genomic profile needs to be clarified. METHODS: Fresh-frozen tissue from primary tumours, synchronous liver metastases and adjacent normal liver was collected from 21 patients and analysed by whole-exome sequencing on the Illumina HiSeq 2500 platform. Gene variants designated as 'damaging' or 'potentially damaging' by Ingenuity software were used for the subsequent comparative analysis. BAM files were used as the input for the analysis of CNAs using NEXUS software. RESULTS: Shared mutations between the primary tumours and the synchronous liver metastases varied from 50 to 96%. Mutations in APC, KRAS, NRAS, TP53 or BRAF were concordant between the primary tumours and the metastases. Among the private mutations were well-known driver genes such as PIK3CA and SMAD4. The number of mutations was significantly higher in patients with right- compared to left-sided tumours (102 vs. 66, p = 0.004). Furthermore, right- compared to left-sided tumours had a significantly higher frequency of private mutations (p = 0.023). Similarly, CNAs differed between the primary tumours and the metastases. The difference was mostly comprised of numerical and segmental aberrations. However, novel CNAs were rarely observed in specific CRC-relevant genes. CONCLUSION: The examined primary colorectal tumours and synchronous liver metastases had multiple private mutations, indicating a high degree of inter-tumour heterogeneity in the individual patient. Moreover, the acquirement of novel CNAs from primary tumours to metastases substantiates the need for genomic profiling of metastases in order to tailor metastatic CRC therapies. As for the mutational status of the KRAS, NRAS and BRAF genes, no discordance was observed between the primary tumours and the metastases.

Growth pattern of colorectal liver metastasis as a marker of recurrence risk.

Despite improved therapy of advanced colorectal cancer, the median overall survival (OS) is still low. A surgical removal has significantly improved survival, if lesions are entirely removed. The purpose of this retrospective explorative study was to evaluate the prognostic value of histological growth patterns (GP) in chemonaive and patients receiving neo-adjuvant therapy. Two-hundred-fifty-four patients who underwent liver resection of colorectal liver metastases between 2007 and 2011 were included in the study. Clinicopathological data and information on neo-adjuvant treatment were retrieved from patient and pathology records. Histological GP were evaluated and related to recurrence free and OS. Kaplan-Meier curves, log-rank test and Cox regression analysis were used. The 5-year OS was 41.8% (95% CI 33.8-49.8%). Growth pattern evaluation of the largest liver metastasis was possible in 224 cases, with the following distribution: desmoplastic 63 patients (28.1%); pushing 77 patients (34.4%); replacement 28 patients (12.5%); mixed 56 patients (25.0%). The Kaplan-Meier analyses demonstrated that patients resected for liver metastases with desmoplastic growth pattern had a longer recurrence free survival (RFS) than patients resected for non-desmoplastic liver metastases (p=0.05). When patients were stratified according to neo-adjuvant treatment in the multivariate Cox regression model, hazard ratios for RFS compared to desmoplastic were: pushing (HR=1.37, 95% CI 0.93-2.02, p=0.116), replacement (HR=2.16, 95% CI 1.29-3.62, p=0.003) and mixed (HR=1.70, 95% CI 1.12-2.59, p=0.013). This was true for chemonaive patients as well as for patients who received neo-adjuvant treatment.

Improved controlled atmosphere high temperature scanning probe microscope.

To locally access electrochemical active surfaces and interfaces in operando at the sub-micron scale at high temperatures in a reactive gas atmosphere is of great importance to understand the basic mechanisms in new functional materials, for instance, for energy technologies, such as solid oxide fuel cells and electrolyzer cells. Here, we report on advanced improvements of our original controlled atmosphere high temperature scanning probe microscope, CAHT-SPM. The new microscope can employ a broad range of the scanning probe techniques including tapping mode, scanning tunneling microscopy, scanning tunneling spectroscopy, conductive atomic force microscopy, and Kelvin probe force microscopy. The temperature of the sample can be as high as 850 °C. Both reducing and oxidizing gases such as oxygen, hydrogen, and nitrogen can be added in the sample chamber and the oxygen partial pressure (pO2) is monitored by an oxygen sensor. We present here some examples of its capabilities demonstrated by high temperature topography with simultaneously ac electrical conductance measurements during atmosphere changes, electrochemical impedance spectroscopy at various temperatures, and measurements of the surface potential. The improved CAHT-SPM, therefore, holds a great potential for local sub-micron analysis of high-temperature and gas induced changes of a wide range of materials.